The low-density lipoprotein receptor (LDL-R) prevents atherosclerosis and hypercholesterolemia through the clearance of the low-density lipoproteins (LDL) in the bloodstream. LDL-R is regulated at the posttranslational level by proprotein convertase subtilisin/kexin type 9a (“PCSK9”). Recently, the knockout of PCSK9 was reported in mice. These mice showed an approximate 50% reduction in the plasma cholesterol levels and showed enhanced sensitivity to statins in reducing plasma cholesterol (Rashid S, et al (2005) Proc Natl Acad Sci 102:5374-5379. Human genetic data also support the role of PCSK9 in LDL homeostasis. Two mutations were recently identified that are presumably “loss-of-function” mutations in PCSK9. The individuals with these mutations have an approximately 40% reduction in the plasma levels of LDL-C which translates into an approximate 50-90% decrease in coronary heart disease. Taken together, these studies indicate that an inhibitor of PCSK9 would be beneficial for lowering plasma concentrations of LDL-C and other disease conditions mediated by PCSK9 and could be co-administered, e.g., with a second agent useful for lowering cholesterol for increased efficacy.